Tom Beril, Dendorfer Andreas, Danser A H Jan
Department of Pharmacology, Room EE1418b, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Int J Biochem Cell Biol. 2003 Jun;35(6):792-801. doi: 10.1016/s1357-2725(02)00273-x.
The beneficial effect of ACE inhibitors in hypertension and heart failure may relate, at least in part, to their capacity to interfere with bradykinin metabolism. In addition, recent studies have provided evidence for bradykinin-potentiating effects of ACE inhibitors that are independent of bradykinin hydrolysis, i.e. ACE-bradykinin type 2 (B(2)) receptor 'cross-talk', resulting in B(2) receptor upregulation and/or more efficient activation of signal transduction pathways, as well as direct activation of bradykinin type 1 receptors by ACE inhibitors. This review critically reviews the current evidence for hydrolysis-independent bradykinin potentiation by ACE inhibitors, evaluating not only the many studies that have been performed with ACE-resistant bradykinin analogues, but also paying attention to angiotensin-(1-7), a metabolite of both angiotensin I and II, that could act as an endogenous ACE inhibitor. The levels of angiotensin-(1-7) are increased during ACE inhibition, and most studies suggest that its hypotensive effects are mediated in a bradykinin-dependent manner.
血管紧张素转换酶（ACE）抑制剂在高血压和心力衰竭治疗中的有益作用，至少部分可能与其干扰缓激肽代谢的能力有关。此外，最近的研究提供了证据，表明ACE抑制剂具有增强缓激肽的作用，这种作用独立于缓激肽水解，即ACE与缓激肽2型（B(2)）受体的“串扰”，导致B(2)受体上调和/或信号转导通路更有效的激活，以及ACE抑制剂对缓激肽1型受体的直接激活。本综述批判性地回顾了目前关于ACE抑制剂不依赖水解增强缓激肽作用的证据，不仅评估了使用ACE抗性缓激肽类似物进行的众多研究，还关注了血管紧张素-(1-7)，它是血管紧张素I和II的代谢产物，可作为内源性ACE抑制剂。在ACE抑制过程中，血管紧张素-(1-7)水平升高，大多数研究表明其降压作用是以缓激肽依赖的方式介导的。
